Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000809907 | SCV000950089 | pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2018-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 182 of the HSPB1 protein (p.Pro182Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with hereditary motor neuropathy (PMID: 16155736). ClinVar contains an entry for this variant (Variation ID: 7483). This variant has been reported to affect HSPB1 protein function (PMID: 25220807). This variant disrupts the p.P182 amino acid residue in HSPB1. Other variant(s) that disrupt this residue have been observed in individuals with HSPB1-related conditions (PMID: 18325928, 27816334, 29381233), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000007911 | SCV000028116 | pathogenic | Distal hereditary motor neuronopathy type 2B | 2005-01-01 | no assertion criteria provided | literature only |